The V Protein of Mumps Virus Plays a Critical Role in Pathogenesis

Xu, Ping; Luthra, Priya; Li, Zhuo; Fuentes, Sandra; D'Andrea, James Alexander; Wu, Jianguo; Rubin, Steven A.; Rota, Paul A.; He, Biao

doi:10.1128/jvi.06019-11

Cited by 37 publications

(39 citation statements)

References 39 publications

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“…In addition, our results showed that IL-6 and IFN peaked early, on day 1 of admission ( Figure 2). Previous publications have shown the critical roles of IL-6 and IFN in viral infections such as in mumps [19][20][21][22], results that are consistent with our findings in varicella infections. These cytokines may be used as serum markers to make early diagnosis of skin infections or liver damage in varicella and to take early measures during the course of the disease.…”

Section: Discussionsupporting

confidence: 93%

Cytokine levels are associated with the severity of varicella infections

Hao

Wang

et al. 2015

J Infect Dev Ctries

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Introduction: Varicella is a highly contagious disease. Epidemics of varicella are seen every year globally and present a threat to public health, especially in China and other developing countries. Methodology: Clinical and laboratory findings of 865 varicella patients admitted to Beijing You'an Hospital, China, between January 2011 and December 2013 were collected and analyzed. Patients with isolated complication were grouped as SI (skin infection, n = 132) and LD (liver damage, n = 89). Two hundred and one patients without complications were grouped as control (mild group). Levels of T-cell subtypes and eight serum cytokines and were also tested. Levels of IFN and IL-6 were monitored prospectively in another 12 grouped patients. Results: SI was complicated in 21.7% (188/865) of varicella cases, and LD was complicated in 16.8% (145/865). The rates of SI and LD in varicella patients increased rapidly in the past three years. No laboratory findings were associated with SI or LD (all p > 0.05). IL-6 and IFN levels were correlated with amniotic membrane extract (AME) (p = 0.044 and p = 0.038). Their levels peaked at day 1 of admission, and then started to decline. Conclusions: The incidence of serious complications has become more common in recent years. IL-6 and IFN may possibly be used as early serum markers for identifying patients at risk of developing complications such as skin infections in varicella.

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Section: Discussionsupporting

confidence: 93%

Cytokine levels are associated with the severity of varicella infections

Hao

Wang

et al. 2015

J Infect Dev Ctries

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“…A new mumps vaccine that matches circulating strains (for instance, genotype G in the U.S. outbreaks) may be ideal. We have used a reverse genetics system to develop novel mumps vaccine candidates based on genotype G by introducing specific mutations in the genome of MuV, such as deletion of SH and V (4,11). One challenge for generating a vaccine is to obtain a virus that grows well in tissue culture cells for vaccine production purposes and is also attenuated in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…Four days later, media were transferred to fresh Vero cell monolayers and propagated further. When syncytium formation was observed, media were collected and used for plaque assays in Vero cells as previously described (11). Single plaques were selected and further amplified in Vero cells.…”

Section: Methodsmentioning

confidence: 99%

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Roles of Serine and Threonine Residues of Mumps Virus P Protein in Viral Transcription and Replication

Pickar

Elson

et al. 2014

J Virol

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Mumps virus (MuV), a paramyxovirus containing a negative-sense nonsegmented RNA genome, is a human pathogen that causes an acute infection with symptoms ranging from parotitis to mild meningitis and severe encephalitis. Vaccination against mumps virus has been effective in reducing mumps cases. However, recently large outbreaks have occurred in vaccinated populations. There is no anti-MuV drug. Understanding replication of MuV may lead to novel antiviral strategies. MuV RNA-dependent RNA polymerase minimally consists of the phosphoprotein (P) and the large protein (L). The P protein is heavily phosphorylated. To investigate the roles of serine (S) and threonine (T) residues of P in viral RNA transcription and replication, P was subjected to mass spectrometry and mutational analysis. P, a 392-amino acid residue protein, has 64 S and T residues. We have found that mutating nine S/T residues significantly reduced and mutating residue T at 101 to A (T101A) significantly enhanced activity in a minigenome system. A recombinant virus containing the P-T101A mutation (rMuV-P-T101A) was recovered and analyzed. rMuV-P-T101A grew to higher titers and had increased protein expression at early time points. Together, these results suggest that phosphorylation of MuV-P-T101 plays a negative role in viral RNA synthesis. This is the first time that the P protein of a paramyxovirus has been systematically analyzed for S/T residues that are critical for viral RNA synthesis. IMPORTANCE Mumps virus (MuV) is a reemerging paramyxovirus that caused large outbreaks in the UnitedStates, where vaccination coverage is very high. There is no anti-MuV drug. In this work, we have systematically analyzed roles of Ser/Thr residues of MuV P in viral RNA synthesis. We have identified S/T residues of P critical for MuV RNA synthesis and phosphorylation sites that are important for viral RNA synthesis. This work leads to a better understanding of viral RNA synthesis as well as to potential novel strategies to control mumps. Mumps virus (MuV) is a human pathogen that causes acute parotitis and is highly neurotropic (1). Invasion of the central nervous system is evident in almost half of all clinical cases, with asceptic meningitis occurring in approximately 10% of cases and encephalitis in less than 1% (1). Even though the mumps vaccine has dramatically reduced disease incidence, large outbreaks have recently occurred in vaccinated populations (2, 3). Over 5,700 mumps cases were reported in a 2006 outbreak that originated at a university in Iowa and spread to 10 other states (2). A mumps outbreak occurred in New York and New Jersey in 2009 to 2010 where 88% of the patients had one dose of mumps vaccine and 75% of patients had two doses (3). There is no antiviral drug for MuV infection. Understanding functions of viral proteins will aid development of antiviral strategies. In this study, a strain of MuV from a recent outbreak in Iowa in 2006 (4), MuV Iowa/US/06 (referred to here as MuV), was used to examine the role of phosphorylation of the M...

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“…In this way, IFN and IL-6 signaling are blocked and the virus can evade both innate and adaptive antiviral responses. [18][19][20][21][22] Furthermore, blockage of the IFN pathway enhances mumps virus replication, as IFN inhibitors promote mumps virus replication in vitro. 23 However, the effect of the V protein on the magnitude of the IFN and IL-6 response is unclear, because IFN and IL-6 levels appear to be elevated in mumps patients, especially in patients with meningitis and/or encephalitis.…”

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confidence: 99%